Summary ? Core C Lack of animal models that accurately mimic human enteric disease limits studies of pathogenesis in the GI tract. Furthermore, elucidating the role of the microbiome in protecting against or exacerbating an infection is complicated by the fact that the commensal microbiota in model animals such as mice, rats, and hamsters are very different from those found in humans. Therefore, there is an urgent need to develop and validate novel pre-clinical models of human enteric disease that more accurately model natural host-pathogen interactions, particularly those in which the impact of the commensal microbes can be evaluated. One strategic mission the Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine is adopting and developing idealized model systems to study host-microbe interactions. The enteroid model is provocative in terms of providing the ability to study host-microbe interactions at a systematic level and incorporating a variety of host and/or commensal perturbations. Development of the enteroids provides an exciting opportunity to advance our understanding of how pathogenic as well as beneficial microorganisms interact with and induce responses from the intestinal epithelium. The goal of the Genomics and Microbiome Core is to provide a centralized facility to meet the comprehensive microbiome needs of all of the investigators involved in this NAMSED proposal and to enable NAMSED investigators to test the hypothesis that commensal microbiota are involved in enteric disease susceptibility and/or protection. Therefore, the long-range objectives of the Microbiome Core are to: (1) characterize how pathogen infection of enteroids impact host and (2) microbe transcription; 3) determine whether enteroids can maintain colonization with individual and communities of commensal microbiota; and 4) characterize how enteroid- association impacts commensal microbiota gene expression. This integrated facility will be cost effective and will ensure reproducibility of genomic, metagenomic, and metatranscriptomic data generated in each of the proposed projects.